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Introduction Although the prevalence of chemotherapy-induced peripheral neuropathy (CIPN) has been reported, the proportion of patients with CIPN who report chronic moderate-to-severe neuropathy or chronic painful neuropathy remains poorly understood, despite its significant impact on patients’ quality of life and treatment outcomes. Methods A systematic review and meta-analysis were conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The primary outcome was the pooled prevalence of chronic (≥3 months) moderate-to-severe CIPN or painful CIPN among patients diagnosed with CIPN. Estimates from each study were transformed using a double-arcsine transformation and pooled in a meta-analysis using an inverse variance heterogeneity model. Subgroup analysis was conducted based on geographical region, sex, chemotherapy regimen, primary cancer type, and funding source; metaregression analysis was conducted based on study design, human development index (HDI), and publication year. Results 76 studies from 29 countries, encompassing 13 635 patients with CIPN, were included. Among patients diagnosed with CIPN, the pooled prevalence of those reporting chronic moderate-to-severe CIPN or painful CIPN was estimated at 47.76% (95% CI 37.50 to 58.08; 95% prediction interval 24.68–71.84). Substantial heterogeneity was observed across studies ( I² =97.45%; 95% CI for I 2 97.15 to 97.72). Subgroup analysis revealed that patients treated with platinum-based agents and taxanes had the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (44.47% and 55.68%, respectively), and among primary cancers, those with breast cancer, multiple myeloma, and lung cancer reported the highest prevalence of chronic moderate-to-severe CIPN or painful CIPN (61.31%, 53.55%, and 50.85%, respectively). Study design, HDI, and publication year were non-significant moderators of prevalence estimates. Based on our Grading of Recommendations, Assessment, Development, and Evaluation assessment, the certainty of evidence was considered “very low.” Sensitivity analysis restricted to studies explicitly measuring painful CIPN (40.78%; 95% CI 29.08 to 52.74) or moderate-to-severe CIPN (49.04%; 95% CI 37.16 to 60.95) yielded similar prevalence estimates. Conclusion This study provides the first comprehensive global estimate of the prevalence of chronic moderate-to-severe CIPN or painful CIPN, highlighting its significant burden on patients worldwide. The variation in prevalence across geographical regions, chemotherapy regimens, and primary cancers underscores the need for tailored management strategies and further research to address potential disparities.

Background/Objectives: The enzyme ubiquitin-specific protease 44 (USP44) is a deubiquitinating enzyme with identified physiological roles as a tumor suppressor and an oncogene. While some binding partners and substrates are known for USP44, the identification of other interactions may improve our understanding of its role in cancer. We therefore performed a proximity biotinylation study that identified products of several known cancer genes that are associated with USP44, including a novel interaction between BRCA2 and USP44. Methods: We expressed a fusion protein that linked USP44 and mutant Escherichia coli biotin ligase BioID in SH-SY5Y neuroblastoma cells. Control experiments were performed using BioID alone. In duplicate experiments, cells were pulsed with biotin and biotinylated proteins were isolated under denaturing conditions and the proteins were identified by mass spectrometry. The resulting list of proteins were analyzed using Enrichr and cross-referenced with the COSMIC Cancer Gene Census. We validated the association with BRCA2 using immunoprecipitation. The role of USP44 in the Fanconi anemia DNA repair pathway was investigated using chromosome analysis of wild-type or Usp44-knockout cells after exposure to mitomycin C. Results: We identified 146 proteins that were selectively retrieved by the USP44 construct and compared with cells expressing the BioID ligase alone, including 15 gene products encoded by genes on tier 1 of the COSMIC Cancer Gene Census, including BRCA2. The association between USP44 and BRCA2 was validated through immunoprecipitation. We tested the functional role of USP44 in the Fanconi anemia DNA repair pathway through chromosome breakage analysis and found that cells lacking USP44 had a significant increase in chromosome breaks and radial chromosomes. We found that high BRCA2 transcript was correlated with poor survival in neuroblastoma, likely due to its tight association with proliferation in these tumors. Conclusions: Our results identified novel potential binding partners and potential substrates for USP44, including several with direct roles in cancer pathogenesis. Our results identified a novel association between BRCA2 and USP44, and a previously unknown role for USP44 in the Fanconi anemia DNA repair pathway that may contribute to its role in cancer.

Indications for and implications of germline genetic testing (GGT) in patients with prostate cancer have expanded over the past decade, particularly related to precision therapies and management. GGT has become the standard of care for many cancers such as breast, ovarian, colorectal, pancreatic, and metastatic prostate cancer, and it is imperative that patients be offered timely and equitable access to testing as it can inform patient-physician shared decision making for management of the current cancer as well as anticipatory guidance for disease progression. Additionally, GGT guides screening for and prevention of secondary malignancies for the patient and cascade testing for at-risk family members. Here, we present data supporting the notion that clinicians should offer all patients with prostate cancer the opportunity to undergo comprehensive GGT for pathogenic germline variants known to be associated with familial cancer and/or known to have implications for treatment and management.

AbstractCurrent US clinical practice guidelines for advanced prostate cancer management contain recommendations based on high‐level evidence from randomized controlled trials; however, these guidelines do not address the nuanced clinical questions that are unanswered by prospective trials but nonetheless encountered in day‐to‐day practice. To address these practical questions, the 2024 US Prostate Cancer Conference (USPCC 2024) was created to generate US‐focused expert clinical decision‐making guidance for circumstances in which level 1 evidence is lacking. At the second annual USPCC meeting (USPCC 2024), a multidisciplinary panel of experts convened to discuss ongoing clinical challenges related to 5 topic areas: biochemical recurrence; metastatic, castration‐sensitive prostate cancer; poly [ADP‐ribose] polymerase inhibitors; prostate‐specific membrane antigen radioligand therapy; and metastatic, castration‐resistant prostate cancer. Through a modified Delphi process, 34 consensus recommendations were developed and are intended to provide clinicians who manage prostate cancer with guidance related to the implementation of novel treatments and technologies. In this report, the authors review the areas of consensus identified by the USPCC 2024 experts and evaluate ongoing unmet needs regarding translational application of the current clinical evidence.

BACKGROUND: The EXCELLENT registry aimed to evaluate the effectiveness of the EMBOTRAP Revascularization Device in an all-comer population in a real-world setting, with a focus on the composition of retrieved clots. METHODS: EXCELLENT is a prospective, global registry of patients with acute ischemic stroke treated with EMBOTRAP as the first-line mechanical thrombectomy device conducted at 34 sites (25 sites contributing clot) from September 2018 to March 2021, utilizing core imaging and central histology laboratories blinded to clinical data, independent 90-day modified Rankin Scale assessment and Clinical Events Committee. RESULTS: After screening 3799 patients, a total of 997 subjects (mean age, 70.0±14.2 years; 51.8% women; 19.7% non-White) were included. The first-pass modified Treatment in Cerebral Infarction (mTICI) ≥2b rate was 64.5% (623/966), first-pass mTICI ≥2c was 39.1% (378/966), and final mTICI ≥2b was 94.5% (931/985). A total of 427/912 (46.8%) patients achieved a 90-day modified Rankin Scale of 0 to 2 or ≤baseline. Embolization to a new territory occurred in 0.2% (2/984), and symptomatic intracranial hemorrhage at 24 hours in 1.6% (16/997). The 90-day mortality was 19.1% (175/918). Device- and/or procedure-related serious adverse events occurred in 5.9% (54/912) through 90 days. The mean RBC percentage of retrieved clots was 45.62±21.372. Among patients who achieved mTICI ≥2b with the first pass, 15.7% (52/331) and 9.7% (32/331), respectively, had RBC-poor (<25%) and RBC-rich (>75%) clots. Patients with no clot retrieved in any procedural pass had a lower percentage of hyperdense or susceptibility vessel sign on baseline imaging (58.9% versus 74.7%; P <0.001), pointing to a potential preprocedure indicator of challenging clot. CONCLUSIONS: The EXCELLENT registry informs real-world practices in mechanical thrombectomy and sheds light on the range of clots effectively retrieved by current technology. This is the first report of detailed patient characteristics where mechanical thrombectomy maneuvers failed to remove any clot material. Although the composition of nonretrievable clots cannot be assessed histologically, the results support the notion that no retrieval may be correlated with imaging findings suggesting clots lower in RBC. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03685578.

Background: Risk stratification for embolism in cardiac myxomas remains poorly explored. Goals: By this meta-analysis we studied the risk factors assicated with embolism among patients with cardiac myxoma. Methods: A comprehensive search was conducted across PubMed, Embase, Cochrane Library, and Google Scholar from their inception until January 2024. Statistical analyses were performed using Cochrane's RevMan 5.4 software. For each risk factor, the pooled odds ratio or mean difference was calculated along with the corresponding 95% confidence interval. Results: We included 18 studies in our analysis with a total population of 2601 out of which 525 patients (20.1%) had at least one episode of embolism. The pooled analyses showed that hypertension (p = 0.001), New York Heart Association I/II (p = 0.03), irregular tumor surface (p <0.00001), hyperlipidemia (p < 0.0001), coronary artery disease (p=0.01), high mean platelet volume (p=0.02), high tumor mobility (p<0.00001), were significantly associated with increased incidence of embolism. Female gender (p = 0.03) was the only risk factor associated with reduced risk. Other factors like smoking, atrial fibrillation, tumor size, age, body mass index (BMI), diabetes, left ventricular ejection fraction (LVEF), left atrial diameter (LAD) were not significantly associated with embolism (p > 0.05). Conclusion: Our study is the first to report significant pooled outcomes for gender, hyperlipidemia, coronary artery disease, mean platelet volume, and tumor mobility in the population discussed. Hypertension, New York Heart Association I/II, irregular tumor surface, hyperlipidemia, coronary artery disease, mean platelet volume and tumor mobility were significantly associated with high risk while female gender was associated with low risk of embolism. Patients with high-risk factors might benefit from early evaluation and definitive treatment (surgery).

Background: Del Nido cardioplegia (DNC) has extensively been used for pediatric population undergoing cardiac surgery. However, its use in adult cardiac surgeries have been limited thus, its benefits are not yet fully known. This analysis was performed to evaluate the impact of DNC versus any other type of cardioplegia in adult patients who are undergoing cardiac surgery. Methods: We systematically searched PubMed, Cochrane Library, and Scopus from database inception till March 2023, and moderate to high-quality randomized controlled trials were included which compared DNC to other cardioplegia. The primary outcome was postoperative stroke and/or transient ischemic attack (TIA). Secondary outcomes included spontaneous rhythm return, postoperative myocardial infarction, all-cause mortality, postoperative atrial fibrillation, defibrillation after coronary reperfusion, postoperative intra-aortic balloon pump, postoperative kidney injury, postoperative low cardiac output syndrome, inotropic support, cardiopulmonary bypass time, cross-clamp time, blood transfusion, cardioplegia volume, hospital stay, intensive care unit stay, mechanical ventilation stay, postoperative left ventricular ejection fraction, and cardiac markers. Results: In this meta-analysis, 13 studies were included with a patient population of 2207. Stroke and/or TIA studies (risk ratio [RR]: 0.54, 95% CI [0.29, 1.00]) and all-cause mortality studies (RR: 1.30, 95% CI [0.66, 2.56]) were insignificant. From the secondary outcomes, spontaneous rhythm return (RR: 1.58, 95% CI [1.02, 2.45]), defibrillation after coronary reperfusion (RR: 0.49, 95% CI [0.30, 0.79]), inotropic support (RR: 0.70, 95% CI [0.57, 0.85]), composite risk of stroke and/or TIA and/or acute kidney injury and mortality (RR: 0.72, 95% CI [0.53, 0.99]), cross-clamp time (mean difference [MD]: −6.01, 95% CI [−11.14, −0.89]), blood transfusion (RR: 0.73, 95% CI [0.60, 0.90]), cardioplegia volume (MD: −537.17, 95% CI [−758.89, −315.45]), troponin T (MD: −1.71, 95% CI [−2.11, −1.32]), creatine phosphokinase-MB (MD: −2.96, 95% CI [−5.84, −0.07]) were significant. Whereas all other secondary outcomes were found to be insignificant. Conclusion: No significant difference was observed between patients undergoing Del Nido administration in comparison to other cardioplegia solutions for the primary outcome, stroke or/and TIA.

Background Randomized clinical trials (RCTs) are considered the gold standard for evaluating the efficacy of healthcare interventions. However, conflicts of interest (COIs) can compromise the scientific integrity in these trials. This study characterized COIs in RCTs on spinal cord stimulation for chronic pain, focusing on the prevalence, disclosure, and monetary value of COIs. Methods This cross-sectional study analyzed RCTs published from January 1, 2013 to July 27, 2023. Primary outcomes included the presence, disclosure, and monetary value of COIs, while secondary outcomes assessed the presence of direct/indirect COIs, sponsor access to data, and associations between COIs and select variables, including journal impact factor, publication year, and study outcomes. Results Of 38 RCTs, 30 (78.9%) reported COIs. On average, 35.6% of authors per RCT had at least one COI, with a mean of 0.7 COIs per author. The mean annual monetary value of COIs was US$41,157.83 per author per RCT. 29 RCTs (76.3%) had undisclosed COIs, with an average of 24.2% of authors per RCT having undisclosed COIs. Sponsor access to data was reported in 67.6% of RCTs. No associations were observed between the mean percentage of authors with COIs and the monetary value of COIs and select dependent variables (impact factor, publication year, and study outcomes). Conclusions A substantial majority of RCTs reported COIs with many authors having undisclosed conflicts, highlighting the need for stringent COI disclosure guidelines to maintain research integrity. Expanding COI registry systems globally and increasing non-industry funding are crucial steps toward enhancing transparency and reducing biases in medical research.